Breast cancer screening has led to substantial reductions in breast cancer mortality in the United States over the past 30 years, but not without unintended harms and shortcomings. Comprehensive, population-based, longitudinal data on the entire screening process can evaluate current screening practices and recommend improvements. The Vermont Prosper Research Center (VPRC) proposes to continue and extend the work of the Vermont Breast Cancer Surveillance System (VBCSS), which has 16 years of experience in collecting Integrated patient risk factor, breast imaging, pathology, treatment, cancer outcome and vital status data. Our first aim is to document the entire breast cancer screening process In community practice across the state of Vermont. The new data collected will add to our 16 years of longitudinal data, which provide the foundation for our proposed research program, data sharing with the Statistical Coordination Center, and collaborations with other PROSPR sites. Second, we will pursue a research program that improves the screening process by developing prognostic markers that can be used to develop personalized management strategies for ductal carcinoma in situ (DCIS). Using longitudinal data on approximately 1400 DCIS cases from the VBCSS, we will seek to identify novel molecular, morphologic, radiologic, and tumor microenvironment markers that can stratify DCIS patients by risk of progression to invasive disease. Our comparative effectiveness analyses will provide a framework by which new DCIS prognostic markers can be evaluated for their potential impacts on the benefits and harms of screening. Third, we will conduct collaborative research with other PROSPR Research Centers, the PROSPR Statistical Coordination Center, the National Cancer Institute, and the larger research community. Our multidisciplinary team of experienced basic, clinical, and population scientists will lead and participate in trans-Network initiatives and ensure the dissemination of our data and study findings. Accomplishment of these aims will provide a rich source of data for use in evaluating and improving current breast cancer screening processes. Success in our research program will fill an urgent need for identification of DCIS prognostic markers that could enable personalized management strategies.